Abstract:Controllable generative models of 3D medical images can synthesize volumes with specified clinical attributes, but this demands samples that are simultaneously high-fidelity, natively 3D, and faithful to the requested conditioning. We present CONFLUX, a latent diffusion model for chest computed tomography (CT): a 3D variational autoencoder compresses each volume, and a rectified-flow transformer generates in the latent space. Generation is conditioned on structured radiological metadata (18 abnormality findings, sex, age, and reconstruction kernel) through adaptive layer normalization. The model leads strong volumetric baselines on tri-planar Frechet distance (FID 32.3 vs. 74.6 for MAISI) while exposing direct control over clinical attributes. To strengthen that control we add an online reinforcement-learning post-training stage (group-relative policy optimization) that rewards how reliably a classifier recovers the requested findings from each generated volume. Judged by a separate, independent classifier, post-training removes 47% of the shortfall relative to real-scan reliability. We release the model and a ~200k synthetic chest-CT dataset with conditioning metadata spanning a wide variety of clinical findings.
Abstract:Diffusion language models, which generate text by denoising a token canvas bidirectionally instead of emitting tokens left to right, have become competitive with autoregressive (AR) generation. Medical foundation models, however, remain almost entirely autoregressive. We adapt a mixture-of-experts diffusion language model, DiffusionGemma-26B, and benchmark it against its same-size AR sibling Gemma-4-26B under an identical LoRA recipe on medical visual question answering datasets, scored by a verbosity-robust LLM judge. Diffusion matches or exceeds AR on all of them, and the finetuned model (3.8B active) is competitive with frontier vision-language models; its decoding is also 3.5-4.4x faster. Beyond this parity, the diffusion model offers a drafting capability AR lacks: any-order infill. Because the canvas is denoised bidirectionally, a radiologist can fix report fragments and have the model fill the text between them, an operation inherent to diffusion but not to autoregression, which is subpar at it. This suits real reports, which are often terse or inconsistent across clinicians and institutions.
Abstract:Recent studies have shown that spatial properties of tumors are critical for understanding disease biology and predicting patient outcomes. These spatial properties are increasingly uncovered through complementary modalities: spatial transcriptomics (ST) captures spatially-resolved molecular states, while hematoxylin and eosin-stained whole slide images (HE) reveal tissue morphology. While approaches are emerging to fuse these modalities, effective methods that learn not only joint representations but also incorporate spatial context across modalities are lacking. Here, we present JASPR (Joint Spatial Representation learning), a self-supervised deep learning framework that integrates HE images and ST data through a cross-modal reconstruction objective that incorporates spatial context within HE images and ST profiles. It employs shared modules to capture universal spatial properties across modalities, while modality-specific experts encode features unique to morphological and genomic data. We train and validate JASPR on breast cancer datasets, demonstrating that its learned joint representation substantially improves HE-based prediction of 9,248 genes and provides prognostic value for breast cancer outcomes.
Abstract:In longitudinal clinical practice, every chest X-ray is read in the context of the patients prior exam, and much of what the radiologist communicates is the change from one visit to the next. To the best of our knowledge, we present the first training-free best-of-N sampling scheme for pre-trained chest X-ray report generators that is explicitly aware of this longitudinal prior to current transition. We call it transition-aware best-of-N sampling, each report is split into sentences and embedded into an unordered set in Rd; each (prior, current) pair is reduced to a fixed-dim directional vector via a set-to-set distance designed to encode the change between the two sets; and candidates are scored by cosine distance from their candidate transition vector to a cached bank of ground-truth training transition vectors, aggregated as min or kNN. We instantiate the framework with four directional set distances (mean-shift, novelty residual, directed-Hausdorff anchor, and cost-weighted optimal transport) and evaluate on a multi-visit AP-PA cohort, running inference under three prompts on three vision-language generators. Transition-aware best-of-N outperforms random selection across the board, with the largest relative gains on the Impression section.
Abstract:Three-dimensional (3D) brain MRI is central to clinical neurology and neuro-oncology, where generative models could augment under-represented cohorts, simulate disease trajectories, and support privacy-preserving data sharing. Latent diffusion has been the go-to solution for modeling imaging data, but it places two competing demands on the tokenizer: encoder embeddings must retain the clinical information that downstream tasks act on, and the decoder must reconstruct anatomically faithful volumes. Existing reconstruction-driven tokenizers achieve the second at the expense of the first. To address this, we introduce a fully volumetric masked-autoencoder (MAE) based tokenizer for 3D brain MRI latent diffusion, decoupling encoder and decoder: a frozen 3D MAE encoder produces clinically informative embeddings, while a dedicated CNN decoder reconstructs voxels from a linear projection of those embeddings. We pretrain the encoder on 35,309 volumes from 18 public cohorts spanning four modalities, ten disease categories, and 200+ acquisition sites, and demonstrate its dual utility in two settings. First, on a 23-task linear-probing benchmark, the encoder outperforms or matches SOTA models (i.e., BrainIAC, BrainSegFounder, and MedicalNet) on 21 of 23 tasks. Second, a conditional diffusion transformer (DiT) trained on these clinically informative embeddings supports both conditional generation across six variables and patient-specific longitudinal forecasting. Together these results establish a single 3D brain-MRI embedding space capable of both downstream clinical tasks and controllable generation.
Abstract:We present OpenMedQ, a medical vision-language model pretrained on the broadest fully-open medical mix to date: 14 datasets totaling ~3.35M pretraining samples spanning pathology, radiology, microscopy, and text-only clinical QA. OpenMedQ reaches state-of-the-art BLEU-1 on PathVQA (75.9), beating Med-PaLM M variants up to 562B parameters (~80x larger), and matches the best reported VQA-MED BLEU-1 (64.5). Its vision encoder, transferred to 8 unseen medical classification benchmarks under an identical downstream recipe, obtains the highest average macro-F1 (0.757) among BiomedCLIP (0.745), PMC-CLIP (0.745), PubMedCLIP (0.746), and a from-scratch baseline (0.616). We release our code and an interactive demo is publicly available as a reproducible baseline for the community.
Abstract:Reinforcement learning with verifiable rewards has rapidly advanced reasoning in vision--language models. However, for chest X-ray report generation, the standard rewards (i.e. exact-match accuracy and step-level processes) are incompatible because the reports consist of unordered and orthogonal findings, rather than a causal reasoning chain. We address this gap with a set-based view: each report is split into sentences and embedded by a frozen sentence transformer, yielding unordered embedding sets. We propose the use of set-to-set distances between generated and reference embeddings as continuous, permutation-invariant rewards. Across two datasets and three vision--language models (Qwen3-VL-2B/4B, Gemma3-4B), post-training with set-to-set distance based rewards via GRPO consistently outperforms supervised fine-tuning and exact-match GRPO on all headline metrics (BERTScore, RadGraph F1 and CheXbert F1 by average \%6.80, \%7.82 and \%4.45 relative improvements respectively). The same set distances also enable test-time best-of-$N$ selection: scoring candidates by their distance to training-report embeddings outperforms random selection on our trained models as well as three closed-source LLMs (Mistral-Small, Gemini-2.5 Flash-Lite, GPT-4o-mini) with on average \%16.4 relative improvement on BERTScore. Used as a streaming signal, they support a more efficient form of test-time scaling: pruning low-scoring candidates mid-generation reduces generated tokens by over 50\% while preserving the Findings quality of full best-of-$N$ selection. Together these results establish set-distance rewards as a unified signal for both post-training and test-time scaling in chest X-ray report generation. Our code is publicly \href{https://anonymous.4open.science/r/Set-Distance-Rewards-CXR-BFDA}{available}.
Abstract:Deep learning methods have demonstrated promising results in predicting BI-RADS scores from mammography images. However, the interpretation of these images can vary, leading to discrepancies even among radiologists. Given the inherent complexity of mammograms, training classification models solely on image labels often yields limited performance. To address this challenge, we curated 2313 mammogram images and their corresponding captions from two mammography atlases. Our proposed approach employs a multi-modal model that uses a pretrained PubMedBERT as the language component. By training this model on image-text pairs with contrastive learning, we enable the vision encoder to absorb the rich information contained in the captions, thereby improving its understanding of mammography findings. We then fine-tune the vision encoder on two datasets for BI-RADS prediction, achieving superior performance compared with models trained without this pretraining, particularly when labeled samples are scarce. The improvement in the 3-class average F1 score ranges from +1% to +14%: a +1% increase with 40K training samples, and a +14% increase with 1K samples. Furthermore, our experiments reveal that 2K image-text pairs from mammography atlases can be more informative than 2K labeled samples for label prediction, with an average margin of +1.1% when more than 10K training samples are available. Overall, our work provides a vision-language model for mammography and highlights the value of textual information from mammography atlases. In addition, we publicly release preprocessed mammography images of the TEKNOFEST dataset. The training code, pre-trained model weights, data extraction scripts, and the released dataset are publicly available at: https://github.com/igulluk/MAM-CLIP
Abstract:Medical vision-language datasets are often limited in size and biased toward negative findings, as clinicians report abnormalities mostly but might omit some positive/neutral findings because they might be considered as irrelevant to the patient's condition. We propose a self-supervised data enrichment method that leverages semantic clustering of report sentences. Then we enrich the findings in the medical reports in the training set by adding positive/neutral observations from different clusters in a self-supervised manner. Our approach yields consistent gains in supervised fine-tuning (5.63%, 3.04%, 7.40%, 5.30%, 7.47% average gains on COMET score, Bert score, Sentence Bleu, CheXbert-F1 and RadGraph-F1 scores respectively). Ablation studies confirm that improvements stem from semantic clustering rather than random augmentation. Furthermore, we introduce a way to incorporate semantic cluster information into the reward design for GRPO training, which leads to further performance gains (2.78%, 3.14%, 12.80% average gains on COMET score, Bert score and Sentence Bleu scores respectively). We share our code at https://anonymous.4open.science/r/SemEnrich-75CF
Abstract:Spatial transcriptomics enables spatial gene expression profiling, motivating computational models that capture spatially conditioned regulatory relationships. We introduce SAGE-FM, a lightweight spatial transcriptomics foundation model based on graph convolutional networks (GCNs) trained with a masked central spot prediction objective. Trained on 416 human Visium samples spanning 15 organs, SAGE-FM learns spatially coherent embeddings that robustly recover masked genes, with 91% of masked genes showing significant correlations (p < 0.05). The embeddings generated by SAGE-FM outperform MOFA and existing spatial transcriptomics methods in unsupervised clustering and preservation of biological heterogeneity. SAGE-FM generalizes to downstream tasks, enabling 81% accuracy in pathologist-defined spot annotation in oropharyngeal squamous cell carcinoma and improving glioblastoma subtype prediction relative to MOFA. In silico perturbation experiments further demonstrate that the model captures directional ligand-receptor and upstream-downstream regulatory effects consistent with ground truth. These results demonstrate that simple, parameter-efficient GCNs can serve as biologically interpretable and spatially aware foundation models for large-scale spatial transcriptomics.